Time to face the fats : What can mass spectrometry reveal about the structure of lipids and their interactions with proteins?

Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

Epithelial mesenchymal transition traits in human breast cancer cell lines

Epithelial mesenchymal transition (EMT) has long been associated with breast cancer cell invasiveness and evidence of EMT processes in clinical samples is growing rapidly. Genome-wide transcriptional profiling of increasingly larger numbers of human breast cancer (HBC) cell lines have confirmed the existence of a subgroup of cell lines (termed Basal B/Mesenchymal) with enhanced invasive properties and a predominantly mesenchymal gene expression signature, distinct from subgroups with predominantly luminal (termed Luminal) or mixed basal/luminal (termed Basal A) features (Neve et al Cancer Cell 2006). Studies providing molecular and cellular analyses of EMT features in these cell lines are summarised, and the expression levels of EMT-associated factors in these cell lines are analysed. Recent clinical studies supporting the presence of EMT-like changes in vivo are summarised. Human breast cancer cell lines with mesenchymal properties continue to hold out the promise of directing us towards key mechanisms at play in the metastatic dissemination of breast cancer.

Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice : real-time PCR quantitation

Orthotopic or intracardiac injection of human breast cancer cell lines into immunocompromised mice allows study of the molecular basis of breast cancer metastasis. We have established a quantitative real-time PCR approach to analyze metastatic spread of human breast cancer cells inoculated into nude mice via these routes. We employed MDA-MB-231 human breast cancer cells genetically tagged with a bacterial β-galactosidase (Lac-Z) retroviral vector, enabling their detection by TaqMan® real-time PCR. PCR detection was linear, specific, more sensitive than conventional PCR, and could be used to directly quantitate metastatic burden in bone and soft organs. Attesting to the sensitivity and specificity of the PCR detection strategy, as few as several hundred metastatic MDA-MB-231 cells were detectable in 100 μm segments of paraffin-embedded lung tissue, and only in samples adjacent to sections that scored positive by histological detection. Moreover, the measured real-time PCR metastatic burden in the bone environment (mouse hind-limbs, n = 48) displayed a high correlation to the degree of osteolytic damage observed by high resolution X-ray analysis (r2 = 0.972). Such a direct linear relationship to tumor burden and bone damage substantiates the so-called 'vicious cycle' hypothesis in which metastatic tumor cells promote the release of factors from the bone which continue to stimulate the tumor cells. The technique provides a useful tool for molecular and cellular analysis of human breast cancer metastasis to bone and soft organs, can easily be extended to other cell/marker/organ systems, and should also find application in preclinical assessment of anti-metastatic modalities.

Art of sleeping - "Like a Thief"

Research background Art of Sleeping’s “Like a Thief” is an EP of popular music produced at Airlock studios and released in 2012 by the record label Dew Process. “Like a Thief” contributes to studies in the field of music production, as well as furthering research into the role of of national radio play in the development of emerging musicians and artists. Using Australian bands such as Boy and Bear as a reference point, the EP showcases the vocal range of Caleb Hodges and investigates possibilities in extending the modes of musicality possible within the recording studio through use of multiple layering of processed keyboards and electric guitar. Scholars such as Ben Eltham and journalists such as Everett True have written about the importance of the support of Australia’s national youth broadcaster Triple J in the early stages of a band’s development. The approach of the production of the EP was conceived with this agenda in mind, and asked, what can we learn about the relationships between popular music production, distribution and consumption, and the role that national public radio has come to play in the Australian context? Research contribution This project has identified that certain avenues of the music industry continue to aligned with Triple J airplay, that these avenues play an important role in the level of success that artists are likely to achieve, and that targeted understanding of music production techniques and aesthetics may contribute to success in this regard. Research significance The EP’s two singles were both in the top 100 most frequently played tracks on Triple J in 2012, and the band were able to leverage this exposure in securing a record deal with Dew Process, along with being selected as part of the competitive peer review process for festival performances such as Splendour in the Grass. The work received positive peer reviews, with indieshuffle writing: “Brisbane's Art of Sleeping are a truly talented band. … the five-piece gained plenty of local attention earlier this year with their stunning single "Empty Hands.” This was the first single off their new EP, Like a Thief, which was produced by the renowned Yanto Browning (The Medics, The Jungle Giants) … The EP includes five tracks of incredible power and sentiment … Title track "Like a Thief” is … [a] standout, again a vast and expansive song which showcases the band's completeness”

Decoupling 2 : technologies, opportunities and policy options

This report was produced by the Decoupling Working Group of the International Resource Panel. It explores technological possibilities and opportunities for both developing and developed countries to accelerate decoupling and reap the environmental and economic benefits of increased resource productivity. It also examines several policy options that have proved to be successful in helping different countries to improve resource productivity in various sectors of their economy, avoiding negative impacts on the environment. It does not seem possible for a global economy based on the current unsustainable patterns of resource use to continue into the future. The economic consequences of these patterns are already apparent in three areas: increases in resource prices, increased price volatility and disruption of environmental systems. The environment impacts of resource use are also leading to potentially irreversible changes to the world’s ecosystems, often with direct effects on people and the economy – for example through damage to health, water shortages, loss of fish stocks or increased storm damage. But there are alternatives to these scary patterns. Many decoupling technologies and techniques that deliver resource productivity increases as high as 5 to 10-fold are already available, allowing countries to pursue their development strategies while significantly reducing their resource footprint and negative impacts on the environment. This report shows that much of the policy design “know-how” needed to achieve decoupling is present in terms of legislation, incentive systems, and institutional reform. Many countries have tried these out with tangible results, encouraging others to study and where appropriate replicate and scale up such practices and successes.

Engendering the responsibility to protect : women and the prevention of mass atrocities

This article explores the relationship between the Responsibility to Protect (R2P) and the pursuit of the so-called ‘Women, Peace and Security’ (WPS) agenda at the UN. We ask whether the two agendas should continue to be pursued separately or whether each can make a useful contribution to the other. We argue that while the history of R2P has not included language that deliberately evokes the protection of women and the promotion of gender in preventing genocide and mass atrocities, this does not preclude the R2P and WPS agendas becoming mutually reinforcing. The article identifies cross-cutting areas where the two agendas may be leveraged for the UN and member states to address the concerns of women as both actors in need of protection and active agents in preventing and responding to genocide and mass atrocities, namely in the areas of early warning.

Supply, demand, and equilibrium in the market for CRNAs

This study determined the current trends in supply, demand, and equilibrium (ie, the level of employment where supply equals demand) in the market for Certified Registered Nurse Anesthetists (CRNAs). It also forecasts future needs for CRNAs given different possible scenarios. The impact of the current availability of CRNAs, projected retirements, and changes in the demand for surgeries are considered in relation to CRNAs needed for the future. The study used data from many sources to estimate models associated with the supply and demand for CRNAs and the relationship to relevant community and policy characteristics such as per capita income of the community and managed care. These models were used to forecast changes in surgeries and in the supply of CRNAs in the future. The supply of CRNAs has increased in recent years, stimulated by shortages of CRNAs and subsequent increases in the number of CRNAs trained. However, the increases have not offset the number of retiring CRNAs to maintain a constant age in the CRNA population. The average age will continue to increase for CRNAs in the near future despite increases in CRNAs trained. The supply of CRNAs in relation to surgeries will increase in the near future.

Corner and finger formation in Hele-Shaw flow with kinetic undercooling regularisation

We examine the effect of a kinetic undercooling condition on the evolution of a free boundary in Hele--Shaw flow, in both bubble and channel geometries. We present analytical and numerical evidence that the bubble boundary is unstable and may develop one or more corners in finite time, for both expansion and contraction cases. This loss of regularity is interesting because it occurs regardless of whether the less viscous fluid is displacing the more viscous fluid, or vice versa. We show that small contracting bubbles are described to leading order by a well-studied geometric flow rule. Exact solutions to this asymptotic problem continue past the corner formation until the bubble contracts to a point as a slit in the limit. Lastly, we consider the evolving boundary with kinetic undercooling in a Saffman--Taylor channel geometry. The boundary may either form corners in finite time, or evolve to a single long finger travelling at constant speed, depending on the strength of kinetic undercooling. We demonstrate these two different behaviours numerically. For the travelling finger, we present results of a numerical solution method similar to that used to demonstrate the selection of discrete fingers by surface tension. With kinetic undercooling, a continuum of corner-free travelling fingers exists for any finger width above a critical value, which goes to zero as the kinetic undercooling vanishes. We have not been able to compute the discrete family of analytic solutions, predicted by previous asymptotic analysis, because the numerical scheme cannot distinguish between solutions characterised by analytic fingers and those which are corner-free but non-analytic.

Shared generation of pseudo-random functions

In Crypto’95, Micali and Sidney proposed a method for shared generation of a pseudo-random function f(·) among n players in such a way that for all the inputs x, any u players can compute f(x) while t or fewer players fail to do so, where 0⩽tcontinue the work of Micali and Sidney. We first provide a general framework for shared generation of pseudo-random function using cumulative maps. We demonstrate that the Micali–Sidney scheme is a special case of this general construction. We then derive an upper and a lower bound for d. Finally we give a simple, yet efficient, approximation greedy algorithm for generating the secret seeds S in which d is close to the optimum by a factor of at most u ln 2.

Shared generation of pseudo-random functions with cumulative maps

In Crypto’95, Micali and Sidney proposed a method for shared generation of a pseudo-random function f(·) among n players in such a way that for all the inputs x, any u players can compute f(x) while t or fewer players fail to do so, where 0 ≤ t < u ≤ n. The idea behind the Micali-Sidney scheme is to generate and distribute secret seeds S = s1, . . . , sd of a poly-random collection of functions, among the n players, each player gets a subset of S, in such a way that any u players together hold all the secret seeds in S while any t or fewer players will lack at least one element from S. The pseudo-random function is then computed as where f s i (·)’s are poly-random functions. One question raised by Micali and Sidney is how to distribute the secret seeds satisfying the above condition such that the number of seeds, d, is as small as possible. In this paper, we continue the work of Micali and Sidney. We first provide a general framework for shared generation of pseudo-random function using cumulative maps. We demonstrate that the Micali-Sidney scheme is a special case of this general construction.We then derive an upper and a lower bound for d. Finally we give a simple, yet efficient, approximation greedy algorithm for generating the secret seeds S in which d is close to the optimum by a factor of at most u ln 2.

Cultural development strategies and urban revitalization

Municipal governments around the globe increasingly turn to museums, performing arts centers, arts districts, and other cultural activities to promote and revitalize their cities. While a significant body of literature examines revitalization strategies that focus primarily around entertainment and commerce, the empirical body of research that specifically investigates the role of cultural strategies in urban redevelopment is still growing. This paper first discusses the development of municipal cultural strategies in the United States, and draws from the literature to outline the characteristics of three different models of such strategies. Second, the paper presents findings from a national survey distributed to municipal agencies involved in the promotion and development of cultural activities and facilities in large and medium‐sized US cities. The survey data indicate that although most agencies are guided by a varied set of goals, entrepreneurial objectives continue to guide the development and support of cultural activities in most cities.

Development and evaluation of the Ontrack Diabetes Program : an automated, web-based type 2 diabetes self-management and dysphoria intervention

This research was conducted in the area of Clinical and Health Psychology. The study involved the development and evaluation of a novel, web-based program aimed to improve Type 2 diabetes self-management and mood. The program was developed as an original technological intervention aimed to improve access to support for rural and remote communities, and is currently being trialled across Australia with a larger sample size. The researcher aims to continue research into the field of clinical psychology, and in particular is interested in working on further interventions to support those with comorbid physical and mental health conditions.

A review of the profile of endothelin axis in cancer and its management

The endothelins and their associated receptors are important controllers of vascular growth, inflammation and vascular tone. In cancer, they have roles in the control of numerous factors in cancer development and progression, including angiogenesis, stromal reaction, epithelial mesenchymal transitions, apoptosis, invasion, metastases and drug resistance. Also, we consider current information on the role of this signalling system in cancer and examine the state of the current cell, animal and clinical trials utilizing endothelin targeted drugs for cancer management. Although targeting the endothelin axis in cell lines and xenografts show some promise in retarding cellular growth, results from limited clinical trials in prostatic cancer are less encouraging and did not offer significant survival benefit. The ability to target both cancer cells and vasculature via endothelin is an important consideration that necessitates the further refining of therapeutic strategies as we continue to explore the possibilities of the endothelin axis in cancer treatment.

Post-disaster reconstruction projects : a logical framework for community participation

In a post-disaster environment, housing reconstruction projects frequently face enormous difficulties due to the various, often apparently ill-considered, internal and external factors. Non-Governmental Organisations (NGOs) operating in post-disaster settings such as in Afghanistan continue to face blame over the failure of reconstruction projects, and worse, they are sometimes even viewed as being corrupt entities. While it is not always possible for NGOs to eliminate or reduce the impact of factors that are outside their control, they certainly can increase the chances of project success by placing considerable emphasis on working more effectively with the affected communities. To achieve maximum community participation in reconstruction projects , this research develops a specific logical framework to guide the process of community participation in post-disaster housing reconstruction in Afghanistan.

Global start-ups profile : one size fits all?

Our research aims to answer the research questions “How do we commonly describe the global start-ups profile as evidenced in prior inductive research?” and “Does this global start-ups profile can effectively explain phenomena in Australian global start-up firms?” We systematically review 29 global start-ups (144 firms) qualitative articles to understand descriptive definitions of global-startup firms. We then triangulate this finding with an Australian high-tech firm. Our contribution is to form a descriptive profile of global start-up phenomenon and raise interesting issues that have potentially fruitful findings for both research and practice. This profile might well be just a deviant from the traditional model that describes how firms establish their footprints, first in their domestic markets followed by moves into cross-border activities. Regardless, government agencies, consultants, and entrepreneurs need to understand the phenomenon. Thus we anticipate that this phenomenon will continue to provide interesting issues for pursuit, both by researchers as well as the practitioner community.